A 90-Day Subchronic Toxicity Study of Submerged Mycelial Culture of Cordyceps cicadae (Ascomycetes) in Rats

Abstract

Cordyceps cicadae is a parasitic fungus that hibernates inside a host (Cicada flammata Dist.) and then grows its fruiting body on the surface of the insect. The complete insect/fungus combination of C. cicadae has been widely applied in Chinese traditional medicine. Recent studies have demonstrated that the medicinal benefits of cultured mycelia are as effective as those found in the wild. However, toxicological information regarding the chronic consumption of C. cicadae mycelia culture is not available. This study was conducted to evaluate the possible toxicity arising from repeated exposure to freeze-dried submerged mycelial culture of C. cicadae for 90 days. A total of eighty 8-week-old Sprague-Dawley rats were divided into 4 groups (10 males and 10 females in each group). C. cicadae was administered daily to animals by gavage at doses of 0, 500, 1000, and 2000 mg/kg body weight for 90 days. No animal deaths occurred and no treatment-related clinical signs were observed during the study period. No statistical differences in body weight gain, relative organ weight, hematology, serum chemistry, and urinalysis were observed. Gross necropsy and histopathological findings indicated that there was no treatment-related abnormality. Based on the results, the no observed adverse effect level of C. cicadae whole broth is determined to be > 2000 mg/kg for male and female Sprague-Dawley rats. The results of this study provides support for the use of C. cicadae fermentation product as a safe agent in functional food.

Prenatal Developmental Toxicity Study of HEA-enriched Cordyceps Cicadae Mycelia in Sprague-Dawley Rats

“…The proximate and HEA analyses have been described in our previous study [20]. Besides HEA, myriocin production is also known to occur in C. cicadae mycelia [28].…”

Prenatal Developmental Toxicity Study of HEA-enriched Cordyceps Cicadae Mycelia in Sprague-Dawley Rats

“…A major concern in the development of functional foods is the accurate assessment of safety for human consumption. Prior to this study, toxicological investigations on HEA-enriched C. cicadae mycelia for a period of 90 days in animals did not show any toxicity up to 2 g/kg oral dose [20]. However, further research is needed to ascertain the effects of HEA-enriched C. cicadae mycelia on prenatal development.…”

“…The negative control group received vehicle treatment (10 ml/kg distilled water daily), the positive control group received 10 ml/kg aspirin (SigmaAldrich) at a dosage of 250 mg/kg body weight (bw) [22] while the three dosages test groups received 10 ml/kg HEA-enriched C. cicadae mycelia at a dose of 500 (low dose), 1,000 (mid dose) and 1,500 (high dose) mg/kg bw, respectively. These dose levels were selected according to the previous chronic toxicity study [20] and were administered orally in the gestation of 6 to 15 days, which is defined as the critical period for early fetal structural development. The day a vaginal plug and/or sperm in vaginal smear were observed was defined as day 0 of pregnancy.…”

“…Proximate, myriocin and HEA analyses Detailed descriptions of the proximate and HEA analyses were presented in the previous study [20]. Myriocin analysis was performed on a liquid chromatography tandem mass chromatography (LC-MS/MS) system.…”

“…Myriocin (ISP-1/thermozymocidin), for example, is a common secondary metabolite purified from cultured filtrates of Isaria sinclairii parasite on the larva of the cicada but is known to induce severe disorders, resulting in the death of the animals at a dose of 1 mg/ml [17]. Although an extensive set of toxicology studies on C. cicadae has been investigated [18][19][20], the teratogenic effects of this insect-fungus complex on the embryo during pregnancy have not been evaluated. This is the first study aims to examine the influence of HEA-enriched C. cicadae mycelia broth on embryo-fetal development in SpragueDawley rats to certify its safety as a functional food ingredient.…”